S. Beck

Enhanced insulin sensitivity in mice lacking ganglioside GM3.

Gangliosides are sialic acid-containing glycosphingolipids that are present on all mammalian plasma membranes where they participate in recognition and signaling activities. We have established mutant mice that lack GM3 synthase (CMP-NeuAc:lactosylceramide α2,3-sialyltransferase; EC 2.4.99.-). These mutant mice were unable to synthesize GM3 ganglioside, a simple and widely distributed glycosphingolipid. The mutant mice were viable and appeared without major abnormalities but showed a heightened sensitivity to insulin. A basis for the increased insulin sensitivity in the mutant mice was found to be enhanced insulin receptor phosphorylation in skeletal muscle. Importantly, the mutant mice were protected from high-fat diet-induced insulin resistance. Our results show that GM3 ganglioside is a negative regulator of insulin signaling, making it a potential therapeutic target in type 2 diabetes.

E-Predict: A computational strategy for species identification based on observed DNA microarray hybridization patterns

DNA microarrays may be used to identify microbial species present in environmental and clinical samples. However, automated tools for reliable species identification based on observed microarray hybridization patterns are lacking. We present an algorithm, E-Predict, for microarray-based species identification. E-Predict compares observed hybridization patterns with theoretical energy profiles representing different species. We demonstrate the application of the algorithm to viral detection in a set of clinical samples and discuss its relevance to other metagenomic applications.

A phase II randomised double-blind placebo-controlled clinical trial investigating the efficacy and safety of ProstateEZE Max: a herbal medicine preparation for the management of symptoms of benign prostatic hypertrophy.

OBJECTIVE The aim of the clinical trial was to evaluate the efficacy and safety of ProstateEZE Max, an orally dosed herbal preparation containing Cucurbita pepo, Epilobium parviflorum, lycopene, Pygeum africanum and Serenoa repens in the management of symptoms of medically diagnosed benign prostate hypertrophy (BPH). DESIGN This was a short-term phase II randomized double-blind placebo controlled clinical trial. SETTING The trial was conducted on 57 otherwise healthy males aged 40-80 years that presented with medically diagnosed BPH. INTERVENTION The trial participants were assigned to receive 3 months of treatment (1 capsule per day) with either the herbal preparation (n = 32) or a matched placebo capsule (n = 25). OUTCOME MEASURES The primary outcome measure was the international prostate specific score (IPSS) measured at baseline, 1, 2 and 3 months. The secondary outcomes were the specific questions of the IPSS and day-time and night-time urinary frequency. RESULTS There was a significant reduction in IPSS total median score in the active group of 36% as compared to 8% for the placebo group, during the 3-months intervention (p < 0.05). The day-time urinary frequency in the active group also showed a significant reduction over the 3-months intervention (7.0-5.9 times per day, a reduction of 15.6% compared to no significant reduction change for the placebo group (6.2-6.3 times per day) (p < 0.03). The night-time urinary frequency was also significantly reduced in the active group (2.9-1.8, 39.3% compared to placebo (2.8-2.6 times, 7%) (p < 0.004). CONCLUSION The herbal preparation (ProstateEZE Max) was shown to be well tolerated and have a significant positive effect on physical symptoms of BPH when taken over 3 months, a clinically significant outcome in otherwise healthy men.

The clinical efficacy of a bovine lactoferrin/whey protein Ig-rich fraction (Lf/IgF) for the common cold: A double blind randomized study

OBJECTIVE The aim of the study was to determine if a bovine lactoferrin/whey protein Ig-rich fraction (Lf/IgF) combination was effective in reducing the number of colds and in turn improving symptom recovery in a cohort of males and females that reported frequently contracting a cold. DESIGN A double blind randomized placebo-controlled clinical trial. SETTING One-hundred and twenty-six participants matched by age, BMI, dietary and physical parameters with self-reported frequent upper respiratory tract symptoms and infections were randomly assigned to receive 600 mg of Lf/IgF or a placebo daily for 90 days. MAIN OUTCOME MEASURES AND RESULTS A total of 90 participants (47 receiving the active and 43 placebo) completed the 90 day trial and 15 completed 45 days participation (6 in the active and 9 in the placebo group). The total number of colds recorded over the study period was 48 for the treatment group versus 112 for the placebo group (p < 0.001). The significant trend was retained when the data was corrected for medications returned (p < 0.001) and for guessing treatment allocations (p < 0.001). Non-parametric analysis demonstrated that the total number of cold-associated symptoms reported by participants that received Lf/IgF was significantly less than those in the placebo group (p < 0.05). Also, total days sick with a cold and cold severity were reduced over the clinical trial period for Lf/IgF over placebo, but the trend was not significant. CONCLUSIONS These findings demonstrate that the Lf/IgF combination significantly decreased the incidence of colds and the cumulative number of cold-related symptoms over placebo. This therapeutic combination may be indicated for the prevention of colds and its most common symptoms in the general population when administered as a preventative supplement.

Dietary recommendations for patients with rheumatoid arthritis: a review

Dietary interventions can assist with the management of disease symptoms that accompany rheumatoid arthritis (RA), such as pain, tender swollen joints, stiffness, and associated disability and disease progression. Dietary interventions have gained widespread appeal for both clinicians and RA patients. Interventions that promote self-help through education can have significant benefits for patients as they negotiate pain and musculoskeletal disability. There is substantial scientific evidence that demonstrates patients diagnosed with RA may benefit from dietary interventions; however, recent systematic reviews remain uncertain about the therapeutic efficacy of dietary manipulation for RA due to clinical trials with a high risk of bias. However, dietary interventions with plausible therapeutic activity may be indicated for reducing RA-associated symptoms, including elimination of foods that may trigger an allergic or intolerant response, introduction of known anti-inflammatory dietary compounds and correction of food, or drug-induced gastrointestinal tract microbiota abnormalities and permeability.

Is it ethical for medical practitioners to prescribe alternative and complementary treatments that may lack an evidence base

TO THE EDITOR: The commissioned article by Pirotta, dealing with the ethics of prescribing alternative complementary treatments that may lack an evidence base,1 contains a number of statements which, if the article had been subjected to peer review, might well have finished up on the cutting-room floor. For example, the statement “it is estimated that as little as a quarter of conventional medicine is based on level-1 evidence” is not backed up by the only monograph cited in support of it.2 Whatever relevance a lack of level-1 evidence may have to the practice of dermatology (for which it is claimed), it plays little part in either modern medicine or the revolutionary advances in surgery, few being the result of a systematic review of multiple well controlled randomised trials. Having said that, the reference to complementary or alternative treatments that lack any evidence base as “medicine” gives a misleading legitimacy to practices that may be — and frequently are — based on cultural, historical or spiritual beliefs, or even just plain wacky approaches to healing. Regrettably, Pirotta adds nothing new to the (uncited) definitive 2004 article by Kerridge and McPhee.3 How times have changed. Not only are doctors now expected to have sufficient knowledge of complementary and alternative medicine to be able to advise their patients of therapeutic alternatives, but we may well have reached the stage where a failure to alert patients of such alternative treatment options may constitute negligence at common law. The New South Wales case of McGroder v Maguire4 is instructive. In that case, the plaintiff, a truck driver, had suffered a neck injury in the course of his employment. Despite a lengthy period of treatment, he continued to suffer from tingling in his arm. The defendant, a general practitioner retained by the plaintiff’s employer, although not having examined the patient, nevertheless referred him to a chiropractor. This referral was held to have been negligent, not because of the referral per se, but because of the patient’s condition. This came to light in the evidence given by a neurosurgeon and orthopaedic surgeon at the trial of the action, both of whom agreed that this case was not one for chiropractic manipulation of the plaintiff’s neck and back. Despite subsequent neurosurgery, the plaintiff became totally incapacitated for work. In the result, both the referring GP and the chiropractor were held to be liable in negligence.